Condensation products of the papaverine series and a process of making same.



senseless AME PIC'IET, or GENEVA, SWITZERLAND, ASSIGNOB TO SOCIETY 01?eanmcan mnostrsYlnsasns, or BASEL, SVJITZE'BLAND.

CONDENSATION PRODUCTS OF THE PAPAVERINE SERIES AND A PBOCESS 'OFYG SAME....L1

No Drawing.

e CH,O% CH.

OCH: Tetrahydropapaverine.

CHzO SH Tetrahydro-papaverinei or acetal OCH:

The nucleus substitution products of tetra hydropapaverine behave inanalogous man- 25 nor. In the most cases it is advantageous tosubstitute for the free aldehydes the cor-4 I responding acetals and toreact with these latter'on the hydropapaverines in presence of a mineralacid. Thereby the acetal is at 30 first saponified by the acid, alcoholand aldehyde or aldehyde hydrate being formed,

Specification of Letters Patent.

Patented Mar. 21,1916.

Application filed July 28, 1914. Seri.a1No., 853;7S7.

aliphatic and'aromaticseries in such a man'- ner, thatthe bivalentaldehyde radical enters betwceri the nitrogen atom and a carbon atom ofthe veratryl residue water being 15 split 03. Thereby a secondhydropyridin nucleus is closed and tetracyclic bases are obtained,having a constitution analogous to that of certain natural alkaloids asfor instance the corydalisalkaloids. 20

The reaction seems to be represented by the following formulas:

C H3 OK W CHL OCH: Methvlen-tetrahydroqmpeverine.

OCHa' 00 H, Ethy iden-tetrahydro-papaverine.

. ficultly soluble in ether and col benzene,

pretty soluble in alcohol and fflm with hydrochloric acid hydrochloridswhich are soluble in water.

' The invention will be illustrated by the following examples Example1': 5 parts of tetrahydropapa- Yerine-hydrochlorid are dissolved in 20parts of pure dilute hydrochloric acid of a density of 1.06 and heatedon a Water bath in an apparatus provided with a reflux cooler. thecourse of an hour, 10 parts of methylal are added by little portions.After cooling, the condensation product (methylentetrahydropapaverine)separates in the form of delicate colorless needles. The yielding is 90per cent. of the theory. The free base, isolated from the hydrochloridby sodium carbonate and recrystallized from dilute alcohol.

forms colorless laminae melting at 157-158 (1., easily soluble inalcohol and chloroform and difiicultly soluble in ether and coldbenzene. -The hydrochlorid melts at 228 to 230 C.

Example 11: 5 parts of tetrahydropapaverine hydrochlorid are dissolvedin parts of pure dilute hydrochloric acid of a density of 1.06 and thesolution obtained is heated on the water bath.- In the course of anhour, 6 parts of acetal are added by little portions and the reactionmass is heated for hour and cooled down. The liquid stiflens to a massof colorless needles constituting the ethylidentetrahydropapaverinehydrochlorid. The base liberated from this hydrochloridby addition ofsodium carbonate and recrystallized from alcohol forms colorless laminaemelting at 148 C.

'EXample III: 5 parts of aminotetrahydropapaverine hydrochlorid(prepared by reducing nitropapaverine with tin and hydrochloric acid)are condensed with acetal in the same conditions as specified in ExampleII. The amino-ethylidentetrahydropapaverine hydrochlorid is obtained ina good yielding andforms little colorless needles assuming after a shorttime a deep ti'nt. The corresponding free base is instable.

Example IV: 5 parts of tetrahydropapaverine hydrochlorid are suspended-in parts of'hydrochloric acid of a density of 1.06 and to thissuspension are added on the water bath 5 parts of diethylbenzacetaiAfter 2 to 3 holes the mass is completely dissolved. The separation ofthe condensationproduct formed viz. of the\benzylidentetrahydropapaverine corresponding to the formula OCH;

l 1. The described process for the manufacture of new condensationproducts of the papaverine series consisting in reacting with aldehydesor hydrdpapaverines.

2. The described process for the ma ufacture of new'condensationproductsof the papaverine'series, consistingin reacting with aldehydes onhydropapaverines in the presence of mineral acids.

for the manufacture of new condensation productsof the 3. The describedprocess papaverine series, consisting in reacting with aldehydes ontetrahydropapaverines 1n the presence of mineral acids.

4. As new products the papa'verine derivatives resulting from thecondensation of hydropapaverine with aldehydes in the presence ofmineral acids, the said productsbeing in the form of their free basesscarcely soluble in Water, difiicultly and cold benzene, pretty solublein alcohol and forming with hydrochloric acid hydrochlorids which aresolublein water...

5. As a new article of manufacture the methylentetrahydropapaverine,which constitutes in the form of itsfree base, colorless soluble inethercrystals melting at 157 158-' 0., easily soluble in alcohol andchloroform and drflicultly soluble in ether and cold benzene,

-- while its hydrochlorid' melts at 228 to In witness whereof Ihavehereunto signed my name this 16th, day of July, 1914:, in the presenceof two subscribing Witnesses.

AME PICTET;

Witnesses:

Louis H. MUNICY, E. Vrnmnns.

